{"doi":"10.1084/jem.20230053","title":"An oncolytic virus–delivered TGFβ inhibitor overcomes the immunosuppressive tumor microenvironment","abstract":"While checkpoint blockade immunotherapies have widespread success, they rely on a responsive immune infiltrate; as such, treatments enhancing immune infiltration and preventing immunosuppression are of critical need. We previously generated αPD-1 resistant variants of the murine HNSCC model MEER. While entirely αPD-1 resistant, these tumors regress after single dose of oncolytic vaccinia virus (VV). We then generated a VV-resistant MEER line to dissect the immunologic features of sensitive and resistant tumors. While treatment of both tumor types induced immune infiltration and IFNγ, we found a defining feature of resistance was elevation of immunosuppressive cytokines like TGFβ, which blunted IFNγ signaling, especially in regulatory T cells. We engineered VV to express a genetically encoded TGFβRII inhibitor. Inhibitor-expressing VV produced regressions in resistant tumor models and showed impressive synergy with checkpoint blockade. Importantly, tumor-specific, viral delivery of TGFβ inhibition had no toxicities associated with systemic TGFβ/TGFβR inhibition. Our data suggest that aside from stimulating immune infiltration, oncolytic viruses are attractive means to deliver agents to limit immunosuppression in cancer.","journal":"The Journal of Experimental Medicine","year":2023,"id":321249,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":45,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.952,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":841691,"name":"Dayana B. Rivadeneira","orcid":"0000-0001-9483-7036","position":1,"is_corresponding":false},{"id":823472,"name":"Konstantinos Lontos","orcid":"0000-0003-0216-3818","position":2,"is_corresponding":false},{"id":1033246,"name":"Victoria Dean","orcid":"0009-0002-9136-3917","position":3,"is_corresponding":false},{"id":1033247,"name":"William G. Gunn","orcid":"0009-0007-9070-7550","position":4,"is_corresponding":false},{"id":614546,"name":"McLane J. Watson","orcid":"0000-0001-5778-7690","position":5,"is_corresponding":false},{"id":1033248,"name":"T. J. Yao","orcid":"0009-0002-8916-5129","position":6,"is_corresponding":false},{"id":1033249,"name":"Drew N. Wilfahrt","orcid":"0000-0001-7364-1931","position":7,"is_corresponding":false},{"id":567444,"name":"Cynthia S. Hinck","orcid":"0000-0002-2163-9378","position":8,"is_corresponding":false},{"id":701893,"name":"Łukasz Wieteska","orcid":"0000-0002-5890-6513","position":9,"is_corresponding":false},{"id":1033940,"name":"Stephen H. Thorne","orcid":null,"position":10,"is_corresponding":false},{"id":398270,"name":"Andrew P. Hinck","orcid":"0000-0003-3320-8054","position":11,"is_corresponding":false},{"id":237079,"name":"Greg M. Delgoffe","orcid":"0000-0002-2957-8135","position":12,"is_corresponding":false},{"id":614549,"name":"Kristin DePeaux","orcid":"0000-0001-8460-727X","position":0,"is_corresponding":true}],"reference_count":49,"raw_metadata":null,"created_at":"2026-07-19T01:07:32.611759Z","pmid":"37552475","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}